A Comparative Study on the Treatment Effect of Lipo-Prostagladin with Hypertension and Diabetes Mellitus in Sudden Sensorineural Hearing Loss Patients / 대한이비인후과학회지

Background and Objectives@#Several drugs which can improve blood flow have been used as treatment options for sudden sensorineural hearing loss (SSNHL) based on the theory that improvement of perfusion into the inner ear will help restore hearing. Lipo-prostaglandin E1 (lipo-PGE1) is a well-known vasodilator that increases peripheral blood flow. The purpose of this study was to investigate the effect of lipo-PGE1 on the recovery of the SSNHL patients with hypertension or diabetes.Subjects and Method We retrospectively analyzed 801 patients who were diagnosed with SSNHL from January 2007 to December 2018. All patients were treated with 48 mg of methylprednisolone for 5 days; some patients received lipo-PGE1, depending on the attending physician. They were divided into four groups according to the presence or absence of hypertension and diabetes. Hearing test was performed again one month after treatment and compared with the test results at the time of diagnosis. @*Results@#As a result of comparing the hearing thresholds before and after the treatment in each group, there was a significant improvement in hearing thresholds in all groups (p<0.001). However, when comparing the effect of lipo-PGE1 for hearing change, there was a significant difference only in the group without any underlying diseases (p=0.016). @*Conclusion@#In this study, we show that lipo-PGE1 was helpful in hearing recovery when used in patients without underlying diseases rather than patients with hypertension or diabetes. Further studies will be needed to determine the therapeutic effects of lipo-PGE1 as an adjuvant treatment in SSNHL patients.

Effects of Exogenous N-Acyl-Homoserine Lactones on Biofilm Formation and Motility in Acinetobacter nosocomialis

One of the major factors contributing to drug resistance in Acinetobacter nosocomialis infections is biofilm development, which is facilitate by quorum-sensing (QS) systems. Quorum sensing by the LuxI and LuxR homologues, AnoI and AnoR, in A. nosocomialis plays a role in biofilm formation and motility of this pathogenic bacterium. The aim of this study was to evaluate the effects of exogenous N-acyl-homoserine lactones (AHLs) on the regulation of biofilm and motility of A. nosocomialis and anoI-deletion mutant. We found that anoR mRNA expression levels in the anoI-deletion mutant were increased in the presence of different types of AHLs compared with that in the absence of exogenous AHL. Among AHLs, C12-HSL appeared to exert the greatest stimulatory effect on biofilm formation and motility. Notably, the anoI-deletion mutant also exhibited significant decreases in expression of the biofilm- and motility-related genes, csuC, csuD and pilT, decreases that were attenuated by addition of exogenous AHLs. Combining the AHL C12-HSL with C6-HSL or C10-HSL exerted synergistic effects that restored the motility phenotype in the anoI-deletion mutant. Taken together, our data demonstrate that C12-HSL may act as an important signaling molecule in A. nosocomialis through regulation of biofilm formation and cell motility, potentially providing a new target for the control of A. nosocomialis infections.

RND efflux pump systems in Acinetobacter, with special emphasis on their role in quorum sensing

Acinetobacter is an important opportunistic, multidrug resistant pathogen causing majority of nosocomial infections worldwide. The multidrug resistance is attributed by a plethora of efflux pumps and the overexpression of the same mediates export of antimicrobial agents. Quorum sensing (QS) is the cell-to-cell communication system in which bacteria produces specific signaling molecules which are transported out to the surrounding environment to communicate with other bacterial cells. It has been noticed that multidrug efflux pumps like resistance-nodulation-cell division (RND) efflux pumps play an important role in QS by exporting these signaling molecules. This review discusses various RND efflux pumps and the current understanding of the interrelationship of RND efflux pumps and QS in Acinetobacter spp. Studies demonstrate that RND efflux pumps could be considered as potential targets to block QS thereby reducing pathogenesis and antibiotic resistance. The known RND efflux pump-mediated quorum quenching strategies for Acinetobacter and other bacterial strains are discussed in detail. Finally, the prospective quorum quenching strategies targeting the transcriptional regulators of RND efflux pumps to inhibit multidrug efflux pumps are addressed.

Clonal and Virulence Distribution of Uropathogenic Escherichia coli Isolated from Children in Korea

Urinary tract infections (UTI) are one of the most frequent infectious diseases. Uropathogenic Escherichia coli (UPEC) are among major pathogens causing UTI. A variety of virulence genes are mainly responsible for the severity of these emerging infection. This study investigate the influences of virulence properties of UPEC isolates with reference to multi-locus sequence typing (MLST). The aim of this study was targeted that investigation of the bacterial pathogenicity associated with UTI in children. A total of 58 UPEC isolates were collected from urine samples from patients with clinical diagnosis of uncomplicated UTI. The MLST of UPEC strains were assessed by methods based on polymerase chain reaction. Motility was evaluated using soft-agar plates. Biofilm formation was analyzed in microtiter dish biofilm formation assay. Cell death assay was analyzed by Annexin V/Phosphatidylserine staining and DNA fragmentation assay. According the result, the predominant sequence type (ST) was ST95 (24.1%) and ST73 (17.2%). There were some difference in virulence gene and antibiotics resistance between ST95 and ST73. The number of 11 (18.9%) isolates were strongly adherent. Based on the detected biofilm formation, these strongly adherent are almost ST73. The ST95 was higher than ST73 in population, but ST95 was lower than ST73 in motility and cell death induction. This study indicated that the UPEC molecular strains are related to some virulence traits. Furthermore, the virulence factors carried by ST73 strains contribute to their abilities to colonize the host and cause disease.

Expert's Consensus on Terminology of Auditory Perceptual Assessment in Voice Disorder / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The purpose of this study was to conduct a preliminary study to develop a standardized guideline for terminology necessary to describe auditory perception qualitatively and quantitatively in voice disorders in the Korean language. SUBJECTS AND METHOD: At first, a subjective questionnaire for Korean translation and definition of 25 auditory perceptual assessment terms proposed by Titze was answered by six speech-language pathologists. Secondly, a new questionnaire that was reconstructed with objective items based on the responses to the first questionnaire was completed by 14 experts who had experience on voice disorder for more than 10 years in Korea. In both questionnaires, the necessity of 32 auditory perceptual assessment terms selected from the 25 terms defined by Titze, GRBAS and CAPE-V was surveyed. RESULTS: The consensus on the Korean translation of auditory perceptual assessment terms was moderate (52.6%) between experts. The terms ‘ rough’ and ‘ shimmer’ demonstrated highest consensus of 85.7%. The consensus on Korean definition of auditory perceptual assessment terms was also moderate (61.6%). The term ‘ yawny’ showed complete consensus (100%). The necessity of auditory perceptual assessment terms varied with terms, but showed high consensus. CONCLUSION: It is necessary to develop and apply various standardized vocabulary terms for clinical evaluation so that they can express pathology and physiological characteristics during vocalization. In addition, despite the fact that there are a lot of auditory-perceptual terms, there is a lack of knowledge about voice quality terms, suggesting the need to promote and educate the developed voice quality terms.

Autophagy in Mycobacterium abscessus Infection

Autophagy is a self-degradative process that removes misfolded or aggregated proteins, clears damaged organelles, as well as eliminates intracellular pathogens playing a role in innate immunity. Mycobacterium abscessus (M. abscessus) has been reported as a causative organism in nearly 80% of the rapid growing mycobacteria (RGM) pulmonary disease. The strain exhibits two different colony types: the smooth (S) one which is considered wild-type and the rough (R) one which is the mutated strain. In accordance to the colony morphology, the S and R types display varying autophagic responses in the host cells with the R type inducing elevated autophagy compared to the S type. The major difference in the autophagy could be based on the bioactive molecules exposed on the surface of the S and R types. Though autophagy has a vital role to play in the clearance of intracellular pathogens, very little is known on the autophagy induced by M. abscessus. It has been known that the intracellular pathogens employ different strategies to evade the autophagic pathway and to survive within the host cells. This review summarizes the most up-to-date findings on autophagy induced by M. abscessus morphotypes and how M. abscessus evades the autophagic machinery to divide and thrive inside the host cells. In addition, the prospects of autophagic machinery in devising new anti-infective strategies against mycobacterial infection is also been discussed.

Autophagy in Mycobacterium abscessus Infection

Autophagy is a self-degradative process that removes misfolded or aggregated proteins, clears damaged organelles, as well as eliminates intracellular pathogens playing a role in innate immunity. Mycobacterium abscessus (M. abscessus) has been reported as a causative organism in nearly 80% of the rapid growing mycobacteria (RGM) pulmonary disease. The strain exhibits two different colony types: the smooth (S) one which is considered wild-type and the rough (R) one which is the mutated strain. In accordance to the colony morphology, the S and R types display varying autophagic responses in the host cells with the R type inducing elevated autophagy compared to the S type. The major difference in the autophagy could be based on the bioactive molecules exposed on the surface of the S and R types. Though autophagy has a vital role to play in the clearance of intracellular pathogens, very little is known on the autophagy induced by M. abscessus. It has been known that the intracellular pathogens employ different strategies to evade the autophagic pathway and to survive within the host cells. This review summarizes the most up-to-date findings on autophagy induced by M. abscessus morphotypes and how M. abscessus evades the autophagic machinery to divide and thrive inside the host cells. In addition, the prospects of autophagic machinery in devising new anti-infective strategies against mycobacterial infection is also been discussed.

Noise-Induced Neural Degeneration and Therapeutic Effect of Antioxidant Drugs

The primary site of lesion induced by noise exposure is the hair cells in the organ of Corti and the primary neural degeneration occurs in synaptic terminals of cochlear nerve fibers and spiral ganglion cells. The cellular basis of noise-induced hearing loss is oxidative stress, which refers to a severe disruption in the balance between the production of free radicals and antioxidant defense system in the cochlea by excessive production of free radicals induced by noise exposure. Oxidative stress has been identified by a variety of biomarkers to label free radical activity which include four-hydroxy-2-nonenal, nitrotyrosine, and malondialdehyde, and inducible nitric oxide synthase, cytochrome-C, and cascade-3, 8, 9. Furthermore, oxidative stress is contributing to the necrotic and apoptotic cell deaths in the cochlea. To counteract the known mechanisms of pathogenesis and oxidative stress induced by noise exposure, a variety of antioxidant drugs including oxygen-based antioxidants such as N-acetyl-L-cystein and acetyl-L-carnitine and nitrone-based antioxidants such as phenyl-N-tert-butylnitrone (PBN), disufenton sodium, 4-hydroxy PBN, and 2, 4-disulfonyl PBN have been used in our laboratory. These antioxidant drugs were effective in preventing or treating noise-induced hearing loss. In combination with other antioxidants, antioxidant drugs showed a strong synergistic effect. Furthermore, successful use of antioxidant drugs depends on the optimal timing of treatment and the duration of treatment, which are highly related to the time window of free radical formation induced by noise exposure.

Seroreactive Mycobacterial Proteins and Lipid in Cattle with Bovine Tuberculosis

Bovine tuberculosis caused by Mycobacterium bovis is a major economic problem in several countries. Antibody responses are useful indicators of M. bovis infection of cattle. To overcome drawback of serological tests with low sensitivity, identification and characterization of multiple serodiagnostic antigens has been required. In this study, the antigens with strong antibody reactivity were searched using fractionation of M. bovis culture filtrate proteins and probing with sera from M. bovis-infected cattle. Twelve proteins which have not previously been described as serologic targets were identified and six proteins among them were expressed in Escherichia coli. The mycobacterial lipoarabinomannan (LAM) with strong seroreactivity in cattle was identified and purified. IgG and IgA responses against the newly identified proteins, the seroreactive proteins with strong antibody reactivity in human tuberculosis, and LAM were compared in M. bovis-infected and non-infected cattle as well as in field samples. In general, sensitivity of the tested antigens was higher in M. bovis-infected cattle than purified protein derivative (PPD) (+) field samples. Although a diverse reactivity and sensitivity according to the antigens were shown, the diagnostic utility of both IgA and IgG antibody to the antigens was similar in M. bovis-infected cattle but utility of IgG antibody was superior to that of IgA in field samples. The antigen with the highest diagnostic value was LAM in both the groups. Other antigens with considerable diagnostic utility were BCG_3488c, BCG_2330, Antigen 85, HspX, and Rv3593 when considered the sensitivity and area under the receiver characteristic curve (AUC) value. These antigens may be valuable candidates to be included in a cocktail test kit for bovine tuberculosis diagnosis.

Genes Involved in the Biosynthesis and Transport of Acinetobactin in Acinetobacter baumannii

Pathogenic bacteria survive in iron-limited host environments by using several iron acquisition mechanisms. Acinetobacter baumannii, causing serious infections in compromised patients, produces an iron-chelating molecule, called acinetobactin, which is composed of equimolar quantities of 2,3-dihydroxybenzoic acid (DHBA), L-threonine, and N-hydroxyhistamine, to compete with host cells for iron. Genes that are involved in the production and transport of acinetobactin are clustered within the genome of A. baumannii. A recent study showed that entA, located outside of the acinetobactin gene cluster, plays important roles in the biosynthesis of the acinetobactin precursor DHBA and in bacterial pathogenesis. Therefore, understanding the genes that are associated with the biosynthesis and transport of acinetobactin in the bacterial genome is required. This review is intended to provide a general overview of the genes in the genome of A. baumannii that are required for acinetobactin biosynthesis and transport.

Speech Recognition in Real-Life Background Noise by Young and Middle-Aged Adults with Normal Hearing

BACKGROUND AND OBJECTIVES: People usually converse in real-life background noise. They experience more difficulty understanding speech in noise than in a quiet environment. The present study investigated how speech recognition in real-life background noise is affected by the type of noise, signal-to-noise ratio (SNR), and age. SUBJECTS AND METHODS: Eighteen young adults and fifteen middle-aged adults with normal hearing participated in the present study. Three types of noise [subway noise, vacuum noise, and multi-talker babble (MTB)] were presented via a loudspeaker at three SNRs of 5 dB, 0 dB, and -5 dB. Speech recognition was analyzed using the word recognition score. RESULTS: 1) Speech recognition in subway noise was the greatest in comparison to vacuum noise and MTB, 2) at the SNR of -5 dB, speech recognition was greater in subway noise than vacuum noise and in vacuum noise than MTB while at the SNRs of 0 and 5 dB, it was greater in subway noise than both vacuum noise and MTB and there was no difference between vacuum noise and MTB, 3) speech recognition decreased as the SNR decreased, and 4) young adults showed better speech recognition performance in all types of noises at all SNRs than middle-aged adults. CONCLUSIONS: Speech recognition in real-life background noise was affected by the type of noise, SNR, and age. The results suggest that the frequency distribution, amplitude fluctuation, informational masking, and cognition may be important underlying factors determining speech recognition performance in noise.

Test-Retest Reliability of Word Recognition Score Using Korean Standard Monosyllabic Word Lists for Adults as a Function of the Number of Test Words

BACKGROUND AND OBJECTIVES: The purpose was to establish the test-retest reliability of word recognition score (WRS) using Korean standard monosyllabic word lists for adults (KS-MWL-A) recently developed based on the international standard for speech audiometry (ISO 8253-3:2012). SUBJECTS AND METHODS: Subjects consisted of 159 adults aged to 18 to 25 years with normal hearing sensitivity. WRSs were obtained in 2 dB steps from the level of speech recognition thresholds to the level of 86% correct responses or greater. After one or two weeks, retest was performed. Correlation, confidence interval (CI) and prediction interval (PI) were calculated for the reliability. RESULTS: Correlation coefficients were 0.88 for 50 test words, 0.76 for 25 and 0.61 for 10 words. Results also showed that 95% CIs and PIs were narrower for 25 and 50 test words than those for 10 test words. CONCLUSIONS: Korean WRS using the KS-MWL-A has high reliability for 25 and 50 test words, but relatively low for 10 words. It suggested that 95% CIs for each test words would be criteria for significant differences in WRS for groups and 95% PIs at each score of WRS could be utilized for a considerable difference for each individual at retest.

Nucleoside Diphosphate Kinase from Microorganisms

Nucleoside diphosphate kinase (Ndk) is ubiquitous and highly conserved multifunctional key enzyme in nucleotide metabolism. It generates nucleoside triphosphates (NTPs) by transfer of gamma-phosphates from nucleoside triphosphates such as ATP or GTP to nucleoside diphosphate. The formation of an autophosphorylated enzyme intermediate is involved in that mechanism. The phosphate is usually supplied by ATP and Ndk activity in different subcellular compartments. Ndk may regulate the crucial balance between ATP and GTP or other nucleoside triphosphates. Ndk is playing an important role in bacterial pathogenesis and emerging evidences recognize multiple roles of Ndk in host-microbe interaction. Here, I review some examples of the role of Ndk in intra- and extracellular microorganism.

Mechanisms and Treatment of Blast Induced Hearing Loss

The main objective of this study is to provide an overview of the basic mechanisms of blast induced hearing loss and review pharmacological treatments or interventions that can reduce or inhibit blast induced hearing loss. The mechanisms of blast induced hearing loss have been studied in experimental animal models mimicking features of damage or injury seen in human. Blast induced hearing loss is characterized by perforation and rupture of the tympanic membrane, ossicular damage, basilar membrane damage, inner and outer hair cell loss, rupture of round window, changes in chemical components of cochlear fluid, vasospasm, ischemia, oxidative stress, excitotoxicity, hematoma, and hemorrhage in both animals and humans. These histopathological consequences of blast exposure can induce hearing loss, tinnitus, dizziness, and headache. The pharmacological approaches to block or inhibit some of the auditory pathological consequences caused by blast exposure have been developed with antioxidant drugs such as 2,4-disulfonyl alpha-phenyl tertiary butyl nitrone (HXY-059, now called HPN-07) and N-acetylcysteine (NAC). A combination of antioxidant drugs (HPN-07 and NAC) was administered to reduce blast induced cochlear damage and hearing loss. The combination of the antioxidant drugs can prevent or treat blast induced hearing loss by reducing damage to the mechanical and neural component of the auditory system. Although information of the underlying mechanisms and treatment of blast induced hearing loss are provided, further and deep research should be achieved due to the limited and controversial knowledge.

Mechanisms and Treatment of Blast Induced Hearing Loss

The main objective of this study is to provide an overview of the basic mechanisms of blast induced hearing loss and review pharmacological treatments or interventions that can reduce or inhibit blast induced hearing loss. The mechanisms of blast induced hearing loss have been studied in experimental animal models mimicking features of damage or injury seen in human. Blast induced hearing loss is characterized by perforation and rupture of the tympanic membrane, ossicular damage, basilar membrane damage, inner and outer hair cell loss, rupture of round window, changes in chemical components of cochlear fluid, vasospasm, ischemia, oxidative stress, excitotoxicity, hematoma, and hemorrhage in both animals and humans. These histopathological consequences of blast exposure can induce hearing loss, tinnitus, dizziness, and headache. The pharmacological approaches to block or inhibit some of the auditory pathological consequences caused by blast exposure have been developed with antioxidant drugs such as 2,4-disulfonyl alpha-phenyl tertiary butyl nitrone (HXY-059, now called HPN-07) and N-acetylcysteine (NAC). A combination of antioxidant drugs (HPN-07 and NAC) was administered to reduce blast induced cochlear damage and hearing loss. The combination of the antioxidant drugs can prevent or treat blast induced hearing loss by reducing damage to the mechanical and neural component of the auditory system. Although information of the underlying mechanisms and treatment of blast induced hearing loss are provided, further and deep research should be achieved due to the limited and controversial knowledge.

Prestin and Motility of the Cochlear Outer Hair Cell

The main objective of this study is to describe the role and function of prestin on cochlear amplification based on the relationship of electromotility and prestin in the outer hair cells (OHCs). After the finding of cochlear active process or amplification, OHCs have been received a lot of attention as a source of the cochlear amplification. In response to acoustic signals, the OHCs produce the receptor potentials resulting in changes in the length of the OHCs called electromotility. The electromotility originates within the lateral wall of the OHCs and relates to the unique structures of the OHCs. The OHC electromotility depends on particles of the lateral plasma membrane due to an area motor in the lateral plasma membrane. Recently, it has been reported that the electromotility requires a voltage-dependent membrane based motor protein, prestin. Prestin means fast in Italian. The presence of prestin is essential for cochlear amplification and electromotility. Prestin is a member of solute carrier 26 anion transporter family. Prestin is associated with the unique structure of the lateral wall of the OHCs. Prestin forms motor complexes with other proteins and lipids of the lateral wall sensing the transmembrane potential and generating force by changing its surface area. Recently, prestin knockout mice have been used to prove the presence of prestin. Prestin is required for electromotility of the OHCs and for cochlear amplification in normal hearing because targeted depletion of prestin in mice leads to loss of OHC electromotility and loss of hearing sensitivity up to 60 dB. In addition, recent studies have shown that the loss of cochlear amplification after intense noise exposure can result from damage to prestin and prestin involves in the process of aminoglycoside-induced apoptosis in OHCs. These show that prestin plays an important role in transducing apoptosis signals in response to antibiotics. Therefore, the presence of prestin is mandatory for cochlear active process and amplification in normal hearing.

Degradation of the Retinoblastoma Tumor Suppressor Protein by the Human Papillomavirus-16 E7 Variants

Human papillomavirus type 16 (HPV-16) plays an etiological role in benign and malignant epithelial tumors. A critical event in HPV transformation of human cells is the inactivation of retinoblastoma protein (pRB) by the E7 protein. The metabolic half-life of pRB is decreased in cells that express high-risk HPV E7 proteins. The present study investigated the frequency of HPV-16 E7 variants in Korean women and compared the pRB degradation activity of E7 variant proteins. Of the 40 HPV-positive specimens from a total of 91 tissue specimens, 21 HPV-16 positive specimens were studied by sequencing analysis to determine the variation of E7 gene. The most frequent E7 variant was N29S (57%). The HPV-16 E7 variant was more prevalent in invasive cervical cancer tissue specimens than in those from low grade clinical stage. The degradation of pRB in HaCaT cells by HPV-16 E7 variant proteins was investigated by western blot analysis. There was no significant difference in pRB degradation activity between the HPV-16 E7 prototype protein and E7 variant proteins. The pRB degradation activity did not differ among HPV-16 E7 variants. These results suggest that the E7-induced degradation of pRB is important in cervical tumorigenesis; however, there was no relation between the pRB degradation activity and the variations in HPV-16 E7 protein among Korean women.

Regulation of Fas and FasL mRNA expression in human astrocytoma cell lines by cytokines

Fas-mediated apoptosis is one of the major mechanisms of programmed cell death. Fas is a transmembrane protein of the nerve growth factor/tumor necrosis factor(TNF-alpha) receptor family which signals apoptotic cell death in susceptible target cells when it reacts with Fas ligand(FasL) or anti-Fas antibody. FasL, which belongs to TNF family, is mainly expressed on the surface of activated T lymphocytes and induces apoptosis of Fas-bearing cell. Astrocytoma is the most common brain tumor, which is usually fatal in its malignant form. Astrocytoma appears to progress without any significant impedance from the immune system, even if intratumoral T cell infiltrations are usually found. In the brain, it has been suggested that astrocytoma cells may potentially deliver a death signal to Fas-bearing cells which include infiltrating leukocytes as well as, paradoxically, astrocytoma cells themselves. In this study, we show that all of the astrocytoma cell lines express both Fas and FasL, which is confirmed by reverse transcription-PCR. Pre-exposure to IFN-gamma, IL-1 and TNF-alpha were found to augment the expression of Fas and FasL. These findings suggest that FasL-induced apoptosis by astrocytoma cells may play a significant role in both the immunosuppression and the regulation of tumor growth within the central nervous system. And also cytokines might play a role in the induction of Fas and FasL in astrocytoma cells.

Neuronal damage confirmed by 1H-MRS in occipital lobe complex partial status epilepticus

A 74-year old woman presented with partial and secondarily generalized status epilepticus lasted for 11 days. Initially her seizures consisted of only unformed visual hallucination, which progressed to formed hallucinations, and then memory disturbance and GTCs. During the period of recurrent formed visual hallucinations, T2-weighted brain MRI revealed high signal intensities in the left occipital lobe. After intravenous phenytoin loading, she did not develop any further GTCs but visual hallucinations persisted. Follow-up MRI performed after complete recovery of seizures showed complete recovery of the previous focal lesions, however, 1H-MRS showed a significant decrease of NAA in the recovered area. These features suggested the neuronal loss in the area of seizure focus, despite the complete recovery of transient focal abnormalities in MRI. This case provides a supportive evidence of neuronal damage even in focal status epilepticus, which stress the importance of early treatment and EEG confirmation of the complete seizure control after the disappearance of clinically obvious seizures.

Change of Dopamine Receptor mRNA Expression in Lymphocyte from Schizophrenic Patients / 신경정신의학

OBJECTIVES: Schizophrenia, commonly developed in adolescence and young adulthood, is one of the most common mental diseases in psychiatry. The etiology or pathogenesis of this disease is uncertain yet, but the dysfunction of dopaminergic system in the brain has been proposed. However, there is no direct evidence of dysfunction of brain dopaminergic systems in schizophrenic patients because the direct assessment of brain dopaminergic systems is almost impossible at present. To overcome this problem, recently founded dopamine receptors and their mRNAs in peripheral lymphocytes was used. The purpose of this study was to define whether the dopamine receptors of peripheral lymphocytes can be the peripheral markers of schizophrenia or not. METHODS: The total numbers of subjects are 87 schizophrenic patients. Among them 44 patients were schizophrenics who had been taking antipsychotic drugs for more than 3 years(medicated patients) 43 schizophrenics who recently are not taken antipsychotic drugs for more than 3 months(drugfree patients) For controls age and sex matched 31 healthy persons were enrolled. Sequential reverse transcription and quantitative polymerase chain reaction of the mRNA were used to investigate the expression of dopamine receptors in peripheral lymphocytes. The gene expression of dopamine receptors were compared in each groups and after starting antipsychotic medicines in drug-free patients, the clinical scales and the dopamine receptors of peripheral lymphocytes were sequentially studied before, 2 weeks after and 8 weeks after medication. RESULTS: 1)In drug-free schizophrenics, D3 dopamine receptor mRNA expression of peripheral lymphocytes was significantly increased comparing with that of controls and drug-medicated schizophrenics and D5 dopamine receptor mRNA expression was increased comparing with only that of drug-medicated schizophrenics. There was no difference between controls and drug-medicated schizophrenics. 2)After antipsychotic medication, dopamine receptors of lymphocytes were increased tendency. 3)Drug-free patients were divided into two groups according to dopamine receptor expression in controls to evaluate the significance of increased dopamine receptor expression. The group of patients with increased dopamine receptor expression had following clinical characteristics. (1)More severe psychiatric symptoms (2)Poor pharmacological response of pBPRS on medicines (3)Severe extrapyramidal side effects after pharmacological treatment CONCLUSION: These results revealed that the molecular biologically determined dopamine receptors of peripheral lymphocytes were reactive, and increased expression of dopamine receptor in peripheral lymphocyte had clinical significance for subgrouping and prognostication. These findings suggested that dopamine receptors of peripheral lymphocyte may represent dopamine receptors of the brain, even the location cannot be determined.